Dolutegravir is the INN of (4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide which has the following chemical formula:

Dolutegravir is known from WO2006/116764 as a compound possessing an antiviral activity, in particular an inhibitory activity against HIV integrase. WO2006/116764 also discloses a tablet prepared using one among the many active ingredients disclosed in this document, microcrystalline cellulose, fumed silicon dioxide and stearic acid. The tablets are prepared by direct compression. WO2006/116764 further discloses a capsule filled with the active ingredient, starch as diluent and magnesium stearate as lubricant.
The sodium salt of dolutegravir and a specific crystalline form of this sodium salt or a hydrate thereof are disclosed in WO2010/068253.
Dolutegravir is practically insoluble and even the known sodium salt of dolutegravir is practically insoluble (solubility below 0.1 mg/ml) in 0.1 N HCl (pH 1.2). At an increasing pH, for example to pH 6.8 in 50 mM KH2PO4 the solubility of the sodium salt of dolutegravir slightly increases but the salt still remains very slightly soluble (1-0.1 mg/ml), only. Due to this very low solubility of the active ingredient the tablets known from WO2006/116764 are of little practical use because the active ingredient will hardly dissolve in the intestine resulting in a low bioavailability.
When repeating the preparation of the tablets disclosed in WO2006/116764, it was furthermore observed that different formulation batches showed differences between the dissolution rates. Additionally, serious difficulties were observed due to an insufficient flowability of dolutegravir and its distinct tendency to sticking. Another disadvantage is the very high volume of this active pharmaceutical ingredient.
Therefore, there is a need for improved solid pharmaceutical dosage forms comprising dolutegravir. In particular, there is a need for solid pharmaceutical dosage forms comprising dolutegravir showing increased dissolution rate of the active ingredient. Furthermore, there is a need for solid pharmaceutical dosage forms comprising dolutegravir which can be manufactured in a reliable and repeatable manner.